Tuesday, April 14, 2015 11:06:30 PM
"...Twelve weeks after human CD34+ HSPC transplantation, high-dose intravenous infection of R5-tropic HIV-1 exists. Treatment group animals maintained CD4+ T-cell levels and reduced viral loads within the peripheral blood and lymphoid tissues. Interestingly, the treatment group of animals displayed background levels of HIV-1 detection within the peripheral blood and lymphoid tissues tested at 14 weeks postinfection. The lack of substantial evidence of HIV-1 detection within the treatment group suggests that LVsh5/C46-modified cells were able to systemically control the infection or potentially completely inhibit the initial viral challenge infection. Furthermore, LVsh5/C46 gene-marking and transgene expression was stable up to 6 months post-transplantation of transduced CD34+ HSPC, and a reporter version of the construct was able to demonstrate significant downregulation of CCR5 in vector-modified cells in vivo. In total, these data support the use of LVsh5/C46 vector as a single dose treatment that can constitutively deliver a therapeutic advantage to cells and allow for long-term engraftment and cellular resistance to HIV-1 pathogenesis in vivo by downregulating CCR5 expression and inhibiting HIV-1 fusion via C46. LVsh5/C46 lentiviral vector is built on decades of HIV-1 gene therapy experience and adds to the developing technologies designed to stably engineer cellular protection from HIV-1 infection such as CCR5-specific nucleases and immunoprophylaxis.16,17,41,42 Currently, underway is a phase 1/2 clinical trial designed to test the safety and feasibility of infusing LVsh5/C46-modified CD34+ HSPC and CD4+ T-cells to treat HIV-1 infection without the use of antiretroviral drugs, and includes the use of busulfan as conditioning to enhance engraftment of LVsh5/C46-modified CD34+ HSPC.43...."
http://www.nature.com/mtna/journal/v4/n4/full/mtna201510a.html
Good luck and GOD bless,
George
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